Organic Acidemias/Acidurias Precision Panel Overview Organic Acidemias/Acidurias (Organic Acid Disorders, OADs) are an important group of inherited metabolic disorders that share a defect in intermediary metabolic pathways of carbohydrate, amino acids and fatty acid oxidation. These enzymatic defects lead to an accumulation of organic acids in tissues and their subsequent excretion in urine. As patients age, the natural progression of organic acidemias lead to intellectual difficulties, increased risk for neurologic complications such as stroke-like episodes and cardiac complications among others. All organic acidurias are inherited in an autosomal recessive pattern. The Igenomix Organic Acidemias/Acidurias Precision Panel can be used to make an accurate and directed diagnosis as well as a differential diagnosis of hyperammonemia and high anion gap metabolic acidosis ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved. Indications The Igenomix Organic Acidemias/Acidurias Precision Panel is indicated for those patients with a clinical suspicion or diagnosis an organic acidemia with or without the following manifestations: - Developmental delay - Mental retardation - Seizures - Lethargy - Coma - Hypotonia - Vomiting - Failure to thrive - Hepatomegaly - Respiratory distress - Cardiac dysfunction Clinical Utility The clinical utility of this panel is: 1 - The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient. - Early initiation of treatment with a multidisciplinary team in the form of nutritional therapy, correction of fluid and electrolyte imbalances, adequate cerebral perfusion. - Risk assessment and genetic counselling of asymptomatic family members according to the mode of inheritance. - Improvement of delineation of genotype-phenotype correlation. Genes & Diseases % GENE GENE OMIM DISEASES INHERITANCE* HGMD** COVERAGE (20X) ABCD4 Methylmalonic Aciduria And Homocystinuria AR 100 8 of 8 ACAD8 Isobutyryl-CoA Dehydrogenase Deficiency AR 100 35 of 35 ACAD9 Acyl-CoA Dehydrogenase Family AR 100 62 of 62 ACADL Long Chain Acyl-CoA Dehydrogenase Deficiency - 100 1 of 1 ACADM Medium Chain Acyl-CoA Dehydrogenase Deficiency AR 99.98 181 of 181 ACADS Shot-Chain Acyl-coa Dehydrogenase Deficiency AR 100 84 of 84 ACADSB 2-Methylbutyryl-CoA Dehydrogenase Deficiency AR 100 21 of 21 ACADVL Very Long Chain Acyl-CoA Dehydrogenase Deficiency AR 100 329 of 329 Alpha-Methylacetoacetic Aciduria, Beta-Ketothiolase ACAT1 AR 100 116 of 116 Deficiency ACSF3 Combined Malonic And Methylmalonic Aciduria AR 100 27 of 27 ADK Hypermethioninemia Due To Adenosine Kinase Deficiency AR 100 15 of 16 Congenital Cataract-Hypertrophic Cardiomyopathy- AGK AR 99.98 33 of 33 Mitochondrial Myopathy Syndrome AGXT Primary Hyperoxaluria Type 1 AR 99.99 210 of 211 Hypermethioninemia With S-Adenosylhomocysteine AHCY AR 100 11 of 11 Hydrolase Deficiency ALDH4A1 Hyperprolinemia Type II AR 100 7 of 7 ALDH5A1 Succinic Semialdehyde Dehydrogenase Deficiency AR 95.41 65 of 69 ALDOB Hereditary Fructose Intolerance AR 100 61 of 65 AMN Imerslund-Grasbeck Syndrome AR 94.02 31 of 32 AMT Glycine Encephalopathy AR 99.98 94 of 96 ARG1 Argininemia AR 100 66 of 68 ASL Argininosuccinic Aciduria AR 100 170 of 170 ASPA Canavan Disease AR 99.56 93 of 94 ASS1 Classic Citrullinemia AR 100 150 of 153 Harel-Yoon Syndrome, Pontocerebellar Hypoplasia, ATAD3A AD,AR 90.98 6 of 8 Hypotonia, And Respiratory Insufficiency Syndrome Mitochondrial Complex V (ATP Synthase) Deficiency Nuclear ATP5F1D AR 98.19 NA of NA Type 5 Mitochondrial Complex V (ATP Synthase) Deficiency Nuclear ATP5F1E AR 100 NA of NA Type 3 Leber Optic Atrophy, Neuropathy, Ataxia, And Retinitis ATP6 Pigmentosa, Mitochondrial DNA-Associated Leigh Syndrome, MI na na Narp Syndrome ATP7B Wilson Disease AR 99.97 989 of 1000 ATPAF2 ATPase Deficiency Nuclear-Encoded AR 100 2 of 2 AUH 3-Methylglutaconic Aciduria Type I AR 99.99 11 of 11 BCKDHA Maple Syrup Urine Disease AR 98.41 96 of 97 BCKDHB Maple Syrup Urine Disease AR 99.99 122 of 123 Bjornstad Syndrome, Gracile Syndrome, Leigh Syndrome, BCS1L AR,MI 99.96 40 of 42 Mitochondrial Complex III Deficiency BTD Biotinidase Deficiency Multiple Carboxylase Deficiency AR 100 261 of 262 CAMKMT 2p21 Microdeletion Syndrome - 99.99 NA of NA Neonatal Severe Primary Hyperparathyroidism, Familial CASR AD,AR 100 445 of 446 Hypocalciuric Hypercalcemia CBS Classic Homocystinuria AR 99.98 192 of 194 CCN6 Progressive Pseudorheumatoid Arthropathy Of Childhood AR 100 NA of NA Methylmalonic Aciduria Due To Transcobalamin Receptor CD320 AR 89 2 of 2 Defect 2 Dent Disease, X-linked Recessive Hypophosphatemic Rickets, CLCN5 Nephrolithiasis With Renal Failure , Low Molecular Weight X,XR,G 99.39 NA of NA Proteinuria With Hypercalciuria And Nephrocalcinosis CLPB 3-Methylglutaconic Aciduria Type 7 AR 96 26 of 26 COA3 Mitochondrial Complex IV Deficiency AR,MI 100 2 of 2 Mitochondrial Complex IV Deficiency, Non-Progressive COA8 Predominantly Posterior Cavitating Leukoencephalopathy AR,MI 86.26 4 of 5 With Peripheral Neuropathy COX10 Leigh Syndrome, Mitochondrial Complex IV Deficiency AR,MI 100 13 of 13 COX14 Mitochondrial Complex IV Deficiency AR,MI 100 1 of 1 COX20 Mitochondrial Complex IV Deficiency AR,MI 99.88 5 of 5 COX6B1 Mitochondrial Complex IV Deficiency AR,MI 100 3 of 3 COX8A Mitochondrial Complex IV Deficiency AR,MI 100 1 of 1 CPS1 Carbamoyl Phosphate Synthetase I Deficiency AR 100 274 of 278 CPT2 Infantile Carnitine Palmitoyltransferase II AD,AR 99.99 116 of 116 CTH Cystathioninuria AR 100 8 of 8 Cystinosis Adult Nonnephropathic, Nephropathic Infantile CTNS AR 100 148 of 153 Cystinosis CUBN Megaloblastic Anemia AR 100 53 of 54 CYP27B1 Hypocalcemic Vitamin D-Dependent Rickets AR 98.45 80 of 80 CYP2R1 Hypocalcemic Vitamin D-Dependent Rickets AR 99.22 6 of 6 D2HGDH D-2-Hydroxyglutaric Aciduria AR 100 42 of 42 DBT Maple Syrup Urine Disease AR 100 73 of 75 DDB2 Xeroderma Pigmentosum Complementation Group E AR 100 17 of 17 Progressive External Ophthalmoplegia With Mitochondrial DGUOK AR 100 68 of 70 DNA Deletions 2-Aminoadipic 2-Oxoadipic Aciduria, Charcot-Marie-Tooth DHTKD1 AD,AR 99.94 25 of 25 Disease, Axonal Type 2q Dihydrolipoamide Dehydrogenase Deficiency, Pyruvate DLD AR 100 26 of 26 Dehydrogenase E3 Deficiency DMGDH Dimethylglycine Dehydrogenase Deficiency AR 99.77 2 of 2 3-Methylglutaconic Aciduria Type V, Dilated Cardiomyopathy DNAJC19 AR 100 6 of 6 With Ataxia EHHADH Fanconi Renotubular Syndrome AD 99.96 1 of 1 Cerebrooculofacioskeletal Syndrome, Xeroderma ERCC2 AR 100 102 of 102 Pigmentosum Complementation Group D Photosensitive Trichothiodystrophy, Xeroderma Pigmentosum ERCC3 AR 99.98 24 of 24 Complementation Group B Fanconi Anemia Complementation Group Q, Xeroderma ERCC4 Pigmentosum Complementation Group F, Cockayne AR 99.68 69 of 72 Syndrome Type 1 Cerebrooculofacioskeletal Syndrome, Xeroderma ERCC5 AR 99.94 58 of 58 Pigmentosum, Complementation Group G ETFA Multiple Acyl-CoA Dehydrogenase Deficiency AR 92.33 32 of 32 ETFB Multiple Acyl-CoA Dehydrogenase Deficiency AR 100 21 of 21 ETFDH Multiple Acyl-CoA Dehydrogenase Deficiency AR 100 221 of 222 ETHE1 Ethylmalonic Encephalopathy AR 100 32 of 33 FAH Tyrosinemia Type 1 AR 100 107 of 108 FARS2 Combined Oxidative Phosphorylation Deficiency AR 99.98 23 of 23 FH Fumarase Deficiency AD,AR 100 229 of 232 Lipid Storage Myopathy Due To Flavin Adenine Dinucleotide FLAD1 AR 97.13 13 of 14 Synthetase Deficiency FTCD Formiminotransferase Deficiency AR 99.83 17 of 17 GALE Galactose Epimerase Deficiency AR 100 29 of 29 GALT Classic Galactosemia AR 100 350 of 350 Cerebral Creatine Deficiency Syndrome, Fanconi Renotubular GATM AD,AR 99.98 21 of 21 Syndrome GCDH Glutaric Acidemia, Glutaryl-CoA Dehydrogenase Deficiency AR 88.74 254 of 254 GCLC Gamma-Glutamyl-Cysteine Synthetase Deficiency AR 99.97 7 of 7 GCSH Glycine Encephalopathy AR 93.52 1 of 1 Neurodevelopmental Disorder With Microcephaly, Cataracts, GEMIN4 AR 99 2 of 2 And Renal Abnormalities GIF Autosomal Recessive Intrinsic Factor Deficiency - 100 NA of NA GLDC Glycine Encephalopathy AR 98.69 359 of 367 GLYCTK D-glyceric Aciduria AR 100 6 of 6 GNMT Glycine N-Methyltransferase Deficiency AR 100 5 of 5 Hyperekplexia, Hereditary , Molybdenum Cofactor Deficiency, GPHN AD,AR 99.2 6 of 6 Complementation Group C 3 GRHPR Primary Hyperoxaluria Type 2 AR 88 51 of 51 GSS Glutathione Synthetase Deficiency AR 100 36 of 38 Central Areolar Choroidal Dystrophy, Cone-Rod Dystrophy, GUCY2D Leber Congenital Amaurosis Type I, Congenital Stationary AD,AR 99.98 248 of 248 Night Blindness HADH 3-Hydroxyacyl-CoA Dehydrogenase Deficiency AR 96.71 26 of 27 HAL Histidinemia - 100 9 of 9 HCFC1 Methylmalonic Acidemia And Homocysteinemia X,XR,G 99.81 NA of NA HGD Alkaptonuria AR 100 158 of 159 HIBCH 3-Hydroxyisobutyryl-CoA Hydrolase Deficiency AR 96.47 27 of 27 HLCS Holocarboxylase Synthetase Deficiency AR 100 47 of 47 HMGCL 3-Hydroxy-3-Methylglutaric Aciduria AR 100 54 of 54 HMGCS2 3-Hydroxy-3-Methylglutaryl-CoA Synthase-2 Deficiency AR 100 37 of 37 Fanconi Renotubular Syndrome With Maturity-Onset Diabetes HNF4A Of The Young, Hnf1b-Related Autosomal Dominant AD 100 172 of 174 Tubulointerstitial Kidney Disease HOGA1 Primary Hyperoxaluria Type 3 AR 100 42 of 42 HPD Hawkinsinuria, Tyrosinemia Type III AD,AR 100 10 of 10 3-Methylglutaconic Aciduria Type VIII, Young-Onset Parkinson HTRA2 AD,AR 99.81 18 of 18 Disease